InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ITK

Summary

InnateDB Protein

IDBP-380839.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ITK

Protein Name

IL2-inducible T-cell kinase

Synonyms

EMT; LPFS1; LYK; PSCTK2;

Species

Homo sapiens

Ensembl Protein

ENSP00000398655

InnateDB Gene

IDBG-55348 (ITK)

Protein Structure

UniProt Annotation

Function

Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. {ECO:0000269PubMed:12186560, ECO:0000269PubMed:12682224, ECO:0000269PubMed:21725281}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:17060314}. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.

Disease Associations

Lymphoproliferative syndrome 1 (LPFS1) [MIM:613011]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma. {ECO:0000269PubMed:19425169}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

T-cell lines and natural killer cell lines.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 45 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	45 [view]
Protein-Protein	44 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding

Biological Process

GO:0001816	cytokine production
GO:0001865	NK T cell differentiation
GO:0002250	adaptive immune response
GO:0006468	protein phosphorylation
GO:0006968	cellular defense response
GO:0007165	signal transduction
GO:0007202	activation of phospholipase C activity
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0032609	interferon-gamma production
GO:0032633	interleukin-4 production
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042110	T cell activation
GO:0045087	innate immune response
GO:0050852	T cell receptor signaling pathway

Cellular Component

GO:0005829	cytosol
GO:0005911	cell-cell junction

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR001562 Zinc finger, Btk motif
IPR001849 Pleckstrin homology domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM